摘要:

Luteinizing hormone-releasing hormone (LHRH)-producing neurons constitute the final pathway for regulation of reproductive endocrine function by the central nervous system. Chronically elevated levels of glucocorticoids exert an inhibitory effect on reproductive function. Although this is thought to be mediated in part via modulation of classical transmitters and peptides which regulate LHRH synthesis and release, it is also possible that glucocorticoids may regulate LHRH neurons directly. We localized glucocorticoid receptors (GR) in LHRH neurons in the rat central nervous system using immunocytochemistry. In males and randomly cycling females 10-24% of LHRH neurons in the medial septum-diagonal bands of Broca, and preoptic regions colocalized nuclear GR. Ovariectomy increased the percentage of GR/LHRH neurons at the level of the organum vasculosum of the lamina terminalis to 34%, half of which showed both nuclear and cytoplasmic GR. Treatment with estradiol reversed this effect. We suggest that the actions of glucocorticoids on reproductive endocrine function are mediated partly through direct modulation of LHRH gene expression and/or release by activated GR. Moreover, GR in LHRH neurons may provide a mechanism by which the gonadal steroid progesterone can affect LHRH neurons directly, despite a lack of progesterone receptors in these neurons.

ISSN:0028-3835    

DOI:10.1159/000126315

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Histamine (HA) stimulates the release of adrenocorticotropic hormone (ACTH) and β-endorphin (β-END) via activation of central postsynaptic H1 or H2 receptors. The effect of HA is indirect and may involve the hypothalamic regulating factors corticotropin-releasing hormone (CRH), arginine vasopressin, or oxytocin (OT). We studied the effect of specific HA H1 or H2 receptor agonists on the concentration of CRH and OT in hypophyseal portal blood in urethane-anesthetized male rats. In addition we investigated the effect of the agonists on ACTH and β-END immunoreactivity in peripheral plasma in conscious male rats pretreated with antiserum to CRH. Intracerebroventricular administration of the H1 receptor agonist 2-thiazolylethylamine (2-TEA) or the H2 receptor agonist 4-methylhistamine (4-MeHA) increased the CRH concentration in pituitary portal blood by 80-90% when compared to preinfusion levels (p < 0.05). Central infusion of saline had no effect. The level of OT in the pituitary portal blood was not affected by 2-TEA or 4-MeHA when compared to saline-treated rats. Intracerebroventricular infusion of 2-TEA or 4-MeHA increased the ACTH concentration in peripheral plasma 3- or 4-fold, respectively (p < 0.01). Pretreatment with a specific CRH antiserum (abCRH) inhibited the responses by 50 and 70%, respectively (p < 0.01). Intracerebroventricular administration of 2-TEA or 4-MeHA increased the β-END immunoreactivity in peripheral plasma 3- or 2-fold, respectively (p < 0.01). These effects were inhibited by 80-90%, when rats were pretreated with abCRH (p < 0.01). We conclude that the ACTH and β-END responses to activation of central histaminergic H1 or H2 receptors are mediated at least in part by hypothalamic CRH, whereas OT does not appear to be invo

ISSN:0028-3835    

DOI:10.1159/000126316

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Insulin-like growth factor I (IGF-I) is shown to be involved in the regulation of pituitary hormones. High IGF-I concentrations were detected in hypothalamus and pituitary during adulthood. This study was undertaken to analyze the cellular distribution of IGF-I in the hypothalamo-hypophyseal system of the adult rat using immunocytochemical procedures. IGF-I was found to be widely distributed throughout the hypothalamus; it was present in the magnocellular neurons of the supraoptic, paraventricular, and accessory nuclei. Moreover, nerve fibres and puncta containing immunoreactive IGF-I were localized in the median eminence and the posterior lobe of the pituitary. These results support possible IGF-I neuromodulatory or neurohormonal action in the hypothalamus on pituitary hormone regulation.

ISSN:0028-3835    

DOI:10.1159/000126317

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Quantitative autoradiography was used to compare melatonin receptors in brain areas and arteries of young (4 weeks old) and adult (14 weeks old) spontaneously hypertensive rats (SHR) to those in age-matched normotensive controls, Wistar-Kyoto (WKY) rats. Age and strain influenced the number of melatonin receptors in an anatomically selective manner, and the most striking changes occurred in arterial receptors. Melatonin receptors were not detectable in the anterior cerebral arteries of adult SHR. In the caudal artery, melatonin receptors decreased with age in both strains, but the decrease was more pronounced in SHR. When compared to age-matched WKY rats, the number of caudal artery receptors was higher in young and lower in adult SHR. The number of melatonin receptors was higher in the area postrema of adult SHR when compared to adult WKY rats, but in the suprachiasmatic nucleus, no such differences between the two strains were present. Alterations in receptor density were not accompanied by changes in binding affinity. Our results indicate that in the rat melatonin receptors show different developmental patterns according to location and that the receptors may be expressed differentially in genetic hypertension.

ISSN:0028-3835    

DOI:10.1159/000126318

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Interleukin-2 (IL-2) alters the release of anterior pituitary hormones at femtomolar concentrations from hemipituitaries incubated in vitro. This cytokine significantly lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulated prolactin (PRL) release, thus demonstrating a reciprocal action of the lymphokine on lactotrophs and gonadotrophs. Since dopamine (DA) is a powerful inhibitor of PRL release, in the present experiments we evaluated possible dose dependent effects of DA on IL-2-induced alterations of the release of PRL, LH, and FSH. Hemipituitaries were incubated with varying concentrations of DA, a combination of IL-2 plus DA, or a combination of haloperidol (1 × 10–5M) with DA for 1 h, followed subsequently by incubation with medium containing only high potassium (K+) to study the effects on depolarization-induced hormone release. DA induced a dose-related, significant lowering of the basal PRL release with a minimal effective dose (MED) of less than 19 nM. The depolarization-induced PRL release was also inhibited, but the MED was 100-fold higher than the MED to inhibit basal PRL release. DA at much higher concentrations (30, 60, and 90 µM) significantly reduced pituitary PRL content. The addition of 0.187, 3.75, 15, or 60 µM DA to IL-2 (10–15 M) blocked IL-2-in duced PRL release. IL-2 (10–15M) produced a significant decrease in LH and FSH release. The combination of 3.75 or 15 µM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the addition of 0.187 µM DA to IL-2 blocked its suppressive influence, and 60 µM DA added to IL-2 produced an additive inhibitory effect. Thus, the interaction of IL-2 and DA is biphasic on LH release. The significant reduction of FSH release induced by IL-2 was blocked in the presence of 0.187, 3.75, 15, or 60 µM DA. DA alone at relatively high concentrations of 30, 60, and 90 µM suppressed basal LH and FSH release. The effects of DA on PRL, LH, and FSH at all doses tested were blocked by the DA receptor blocker, haloperidol which by itself at the concentration tested (1 × 10–5M) had no effect. Thus, the actions of DA at all concentrations tested appear to be mediated via DA receptors. In conclusion, DA was capable of blocking the stimulatory action of IL-2 on PRL release and its inhibitory action on FSH release by a DA receptor mediated action. Only a relatively low concentration of DA (0.187 M) blocked the inhibitory action of IL

ISSN:0028-3835    

DOI:10.1159/000126319

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Quantitative autoradiography was used to evaluate the time course and reversibility of corticosterone (CORT)-induced decreases in binding at 5-HT1A receptors in the dorsal hippocampus, cortex and septum of the male rat. Continuous exposure to high levels of CORT decreased binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin at 5-HT1A receptors in the dentate gyrus and in the oriens and lacunosum moleculare layers of CA4 after 16 to 48 h. CORT-induced decreases in binding were also observed in the dorsal lateral septum after 2-4 days, and in the intermediate lateral septum after 4-8 days of exposure to high levels of CORT. When CORT pellets that had remained in rats for 8 days were removed 3 weeks prior to sacrifice, binding at 5-HT1A receptors increased in comparison to control values in the oriens and lacunosum moleculare layers of CA2, and in layers 4-6 of the parietal/temporal cortex. These increases in binding were associated with very low serum CORT levels, and resembled increases previously observed in those areas in ADX rats. Although removal of CORT reversed the decreases in binding in the septum, no significant increases above control values were observed. Thus, there appear to be differences in the degree of sensitivity in the various brain regions to low and high levels of circulating adrenal steroids.

ISSN:0028-3835    

DOI:10.1159/000126333

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Galanin has been reported to stimulate secretion of GH in humans and rats. Thus, to investigate whether the effect of galanin on GH release is the result of either a stimulation of GH-releasing factor (GRF) and/or an inhibition of somatostatin (SRIF) release, we have evaluated the action of galanin on the release of SRIF and GRF from median eminence (ME) fragments in vitro. The MEs from adult male rats were incubated in Krebs-Ringer bicarbonate-glucose buffer, pH 7.4, at 37°C, in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. Medium was discarded and replaced by medium containing various concentrations of galanin (10–10–10–7M). Galanin stimulated SRIF and GRF release in a dose-related manner. This effect was significant at concentrations varying from 10–8 to 10–7M. To determine the mechanism by which galanin stimulated SRIF and GRF release, MEs were incubated with pimozide (dopaminergic blocker), phentolamine (α-ad-renergic blocker) or naloxone (opioid blocker), at concentrations of 10–6M, and the effect of galanin was then evaluated. Phentolamine and naloxone did not alter the stimulatory effect of galanin, but when galanin was tested with pimozide, the galanin-induced release of SRIF and GRF was blocked. To determine whether the effect of galanin is mediated through D-1 and/or D-2 dopamine receptors, selective antagonists of D-l (SCH 23390) and D-2 receptors (domperidone) were used (10–7M) in the presence of galanin (10–7M). The stimulatory effect of galanin on SRIF release was unaffected by domperidone, although SCH 23390 inhibited galanin-evoked SRIF release. However, galanin-evoked GRF release was completely abolished by either domperidone or SCH 23390. Since GRF stimulates SRIF release in vitro, we hypothesized that the SRIF-stimulating action of galanin might be mediated by GRF accumulating in the static incubation system; however GRF antiserum (1:100) failed to alter this effect. These results demonstrate that galanin stimulates GRF and SRIF from ME fragments in vitro by a dopaminergic mechanism. In vivo, this GRF activates release of GH from the somatotropes. Thus, the stimulation of GRF release by galanin will increase GH release. Since galanin stimulates GH release in vivo, its stimulatory effect on SRIF release via a dopaminergic mechanism was puzzling. Since this effect was not blocked by GRF antiserum, the mediation of the effect by accumulated GRF appears to be ruled out. Therefore, we hypothesize that the effect is mediated by galanin itself acting as a negative feedback, when present in high concentration intrahypothalamically, to stimulate SRIF release. This effect would not be manifest in vivo except at very high secretion rates of galanin since the released galanin would enter the portal vessels instead of remaining in the tissue as in this static incubation sy

ISSN:0028-3835    

DOI:10.1159/000126320

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Sex steroids play an important role in the development and functioning of the central nervous system (CNS); however, the mechanisms by which such hormones exert these effects are not well understood. We addressed the question as to whether sex steroids affect the development of the hypothalamus, at least in part, by acting as a trophic factor to modulate the number of neurons in the hypothalamus. To this end, primary hypothalamic cultures were prepared from the brains of embryonic (day 15) fetuses. Cultures received either 17β-es-tradiol (10–12M) or vehicle 6 h after seeding and everyday throughout the study. As early as 24 h later, cultures receiving 17β-estradiol had significantly more neurons (44%, p < 0.001) than the control cultures. This effect not only continued throughout the duration of the study, but the difference between the two groups increased so that after 5 days, 17β-estradiol-treated cultures had 209% more neurons than control cultures (p < 0.001). Thus, addition of 17β-estradiol to fetal hypothalamic cultures produced a significant increase in the number of neurons surviving in vitro. The presence of glia was not required for this phenomenon, since the number of neurons surviving in glial-free cultures was also significantly increased by the addition of 17β-estradiol. The neuron survival promoting effect of 17β-estradiol was saturable and could be blocked by the estrogen antagonist tamoxifen (10-7M). Testosterone (10–10M), but not the nonaromatizable androgen dihydrotestosterone (10–10M), could mimic the neuron survival-promoting effects of estradiol. Furthermore, estradiol had no significant effect on the in vitro survival of cerebral cortical neurons. These results suggest that one mechanism by which sex steroids may affect the development of the hypothalamus is through the modulation of the number of neurons that survive and that this effect is most likely mediated, at least in part, through the estrog

ISSN:0028-3835    

DOI:10.1159/000126321

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The concentrations in plasma of the biologically active endogenous peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) have not been measured during development or in female rats. By radioimmunoassay, we found that Tyr-MIF-1 -like immunoreactivity (Tyr-MIF-1-LI) was first consistently detectable in plasma when the rat was 5 days old, and then gradually increased to adult concentrations by day 15. In male rats, the levels remained relatively constant for the next 21 months. In female rats, plasma concentrations of Tyr-MIF-l-LI at day 15 were about the same as in male rats. At 6 months of age, however, the concentrations in females decreased by half and by 21 months of life were only about a third of the concentrations found at day 15 or in age-matched males. The differences with age were not due to the length of time of storage of the samples, because another group of rats 1 month old was killed on the same day as 5-day-old rats and still showed several times more Tyr-MIF-1-LI in the plasma; again, no differences were found between male and female rats at either 5 days or 1 month. A single injection of estradiol followed by progesterone lowered the concentrations in 1-month-old male rats. In female rats that were either ovariectomized or sham-ovariectomized, the expected similarity in their plasma concentrations of Tyr-MIF-1-LI was found at 1 month of age. By contrast, at 2 and 12 months of age, ovariectomized rats had several times more Tyr-MIF-1-LI in their plasma than the sham operated female controls, as would be seen in male rats. The results indicate a significant interaction of sex with age in concentrations of Tyr-MIF-l-LI in the plasma of rats.

ISSN:0028-3835    

DOI:10.1159/000126322

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To investigate the role of ∂-opioid receptors in the modulation of growth hormone (GH) secretion, we compared in normal subjects the effect of the highly selective ∂-opioid receptor agonist Deltorphin (DT) on the GH secretion responses to pituitary (GH-releasing hormone, GHRH)- and hypothalamic (insulin-induced hypoglycemia, ΠH)-mediated stimuli. DT blunted the GH response to IIH, whereas it had no effect on the GH response to GHRH. It is concluded that in man DT-induced activation of ∂-opioid receptors exerts an inhibitory action on hypoglycemia-stimulated GH secretion. Based on the lack of an effect of DT on the GH response to GHRH, we suggest that DT may modulate the secretion of GH through suprapituitary mech

ISSN:0028-3835    

DOI:10.1159/000126323

出版商:S. Karger AG    

年代:1992

数据来源: Karger